Nicole D Fleming1, Robert L Coleman2, Celestine Tung3, Shannon N Westin2, Wei Hu2, Yunjie Sun2, Priya Bhosale4, Mark F Munsell5, Anil K Sood2. 1. Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States. Electronic address: nfleming@mdanderson.org. 2. Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States. 3. Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX 77030, United States. 4. Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States. 5. Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States.
Abstract
OBJECTIVES: To assess the tolerability and efficacy of bevacizumab with carboplatin and weekly paclitaxel as first-line adjuvant therapy for advanced stage ovarian cancer. METHODS: After IRB approval, this single-institution, phase II study enrolled patients with stage III or IV epithelial ovarian cancer after primary cytoreductive surgery to treatment with carboplatin (AUC 5), weekly paclitaxel (80mg/m2), and bevacizumab (15mg/kg) every 3weeks for at least 6cycles. The primary endpoint was tolerability of at least 4cycles of therapy, with a target treatment success rate of >60%. Secondary endpoints included progression-free survival (PFS) and response rate. Plasma biomarkers were analyzed by the multiplex ELISA assays. RESULTS: Thirty-three patients were enrolled with 30 evaluable patients receiving at least one cycle of combination treatment. Twenty-three patients (77%) were able to complete at least 4cycles of therapy per protocol, and the posterior probability that the treatment success rate is >60% is 0.77. Twenty-one patients (70%) were able to complete ≥6cycles of therapy. Median PFS was 22.4months for patients with optimal (R0) compared to 16.9months for optimal≤1cm (HR 1.71, 95% CI 0.58-4.98, p=0.33), and 16.9months for suboptimal>1cm (HR 3.75, 95% CI 1.05-13.34, p=0.04) disease. Increases in mean Flt-3L was significantly higher in responders versus non-responders (83.4 vs. 28pg/mL, p=0.05). CONCLUSIONS: Adjuvant bevacizumab with dose-dense chemotherapy is associated with acceptable toxicity and a high likelihood of completing 4cycles of therapy. Dynamic changes in Flt-3L may represent a predictive marker to treatment response.
OBJECTIVES: To assess the tolerability and efficacy of bevacizumab with carboplatin and weekly paclitaxel as first-line adjuvant therapy for advanced stage ovarian cancer. METHODS: After IRB approval, this single-institution, phase II study enrolled patients with stage III or IV epithelial ovarian cancer after primary cytoreductive surgery to treatment with carboplatin (AUC 5), weekly paclitaxel (80mg/m2), and bevacizumab (15mg/kg) every 3weeks for at least 6cycles. The primary endpoint was tolerability of at least 4cycles of therapy, with a target treatment success rate of >60%. Secondary endpoints included progression-free survival (PFS) and response rate. Plasma biomarkers were analyzed by the multiplex ELISA assays. RESULTS: Thirty-three patients were enrolled with 30 evaluable patients receiving at least one cycle of combination treatment. Twenty-three patients (77%) were able to complete at least 4cycles of therapy per protocol, and the posterior probability that the treatment success rate is >60% is 0.77. Twenty-one patients (70%) were able to complete ≥6cycles of therapy. Median PFS was 22.4months for patients with optimal (R0) compared to 16.9months for optimal≤1cm (HR 1.71, 95% CI 0.58-4.98, p=0.33), and 16.9months for suboptimal>1cm (HR 3.75, 95% CI 1.05-13.34, p=0.04) disease. Increases in mean Flt-3L was significantly higher in responders versus non-responders (83.4 vs. 28pg/mL, p=0.05). CONCLUSIONS: Adjuvant bevacizumab with dose-dense chemotherapy is associated with acceptable toxicity and a high likelihood of completing 4cycles of therapy. Dynamic changes in Flt-3L may represent a predictive marker to treatment response.
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